Abstract

Biomarkers are Novel and Revered Tools and Technologies (NORETs) which have helped previous studies anticipate diverse disease conditions and complications as well as provide similarly close prognosis for them. These NORETs in rare but common studies regarding Type 2 Diabetes (T2D) has helped health care professionals and scientists identify health-worthy indications relating to T2D complications and potential risk factors. Biomarkers in its own way debuting in the diagnosis and prognosis of T2D has provided health care professionals with the basic kits of understanding how these diseases manifest from seemingly mild problems which we often times ignore to complicated problems, also indicating possible causes. In this study, the pathophysiology of T2D was subtly exhausted pointing the focus towards the rapidly modifying metabolic manifestations of T2D as well as its risk complications. This study thus reveals the on-going advancement of biomarkers in fully understanding, identifying, diagnosing and treating T2D

Keywords

Introduction

Diabetes in both developed and developing countries of the
world has resulted in severe complications like high blood
pressure, cardiovascular complications, renal dysfunction,
visual malfunctioning, and even blindness. The prevalence of
this disease in question has resulted in excessive spending of
finances and resources for nearly adequate solutions.

It is common news worldwide that diabetes had expansively
affected at least 380-400 million people in the previous years if
not more, and has also resulted to about 4-5 million mortality
in the year 2014 only. The persistent occurrence of diabetes in
its raw form has been predicted to rise rapidly by 2035 [1].

Type 2 Diabetes, (T2D), a type of diabetes, on the other
hand, is as a result of insulin resistance (IR) as well as rapid
malfunctioning of the pancreatic β-cell. The continuous and
relentless persistence of T2D have multiplied its spread and
effects over time now and this is relatively significant to
sedentary lifestyle and unhealthy dieting [2]. In order to
determine the root causes of this reeling disease, we must
closely examine the genetic and environmental factors.
Although some relevant genetic studies have subtly identified
some factors relating to the high risks for T2D, they haven’t yet
provided in details a clear understanding of its biological
functions. However, the early identification of this disease is
paramount in avoiding other risk factors or complications
indicating T2D. So, it is importantly relevant that specific
biomarkers be identified for the quick and safe analysis and
prediction of this prevalent disease, T2D.

When IR decreases rapidly, there is a reciprocal increase in
the production of insulin as well as its continuous presence in
the body without been duly utilised. This is usually termed
hyperinsulinemia and it un-relentlessly leads to the
proliferation of T2D. This will surely occur when the pancreatic
β-cell had suddenly become incompetent in regulating the
insulin production as well as glucose concentration [3]. Three
studies indicated that IR formed the precursor and therapeutic
framework or basis in the disease condition of increased
glucose concentration and similarly potentiated risk for
cardiovascular disease (CVD) and vascular disposition for T2D
occurrences [4-6]. Several biomarkers like the branched-chain
amino acid and micro Ribonucleic acids (mRNAs) have been
exclusively identified in recent studies into-omics, for T2D
[7,8]. More so, studies like those of Yang et al. [9] and
Barazzoni et al. [10] have provided researchers with potential
biomarkers (ghrelin and retinol-binding protein) to work with,
yet, Echouffo-Tcheugui et al. [11] could rarely see through the
loop into T2D risk complications. It would be an outstanding
relief when substantial biological tools in the prediction of T2D
and risk complications as well as its relatives are identified.
This would in no doubt ease better analysis for the effective
prediction of T2D as well as in the administration of relevant
diagnosis and prognosis and this was probably in Assarsson’s
et al. collaborative thinking in providing the Proximity Extension Assay (PEA). This positive thinking has played a role
in improving the comparative studies of protein in their
cumbersome nature within very small samples [12].

Delving into the concept of biomarkers, we find that
biomarkers have long painted the walls of qualitative and
quantitative research over the years now. Several countries
have participated in the biomarker revolution in expressly
every biological assay. We discovered from these sole
benefactors of the advances of biomarkers in the early ages of
research development had noted that the sweet taste, which
was actually raw and concentrated indicated the presence of
excessive sugar which in turn contributed to the basis for
diabetes test using urine. HbA1c, a glycohemoglobin value
culminated an important criterion for the distinct regulation of
blood sugar levels in both type diabetes (T1D and T2D). This
HbA1c value spontaneously retains the sugar data of the
patient in question and processes the acquired data based on
the concentration levels for some time, even lasting weeks,
but when the blood sugar eventually eases down or better yet
improved upon, the elevated values comes falling down.

Ron Zimmer [13], described biomarker as proteins, cell,
molecules, genes even enzymes or hormones which could be
measured in their own capacity, religiously assessed as a
primary indicator for the homeostatic processes and responses
aimed at delivering means to solving physiologic
complications. Houlka [14] had noted that biomarkers though
expressly vague have been a major experimental tool by
researchers and scientists to analytically study human
diseases. Desai [15] expressly reported that ‘blood pressure’
though a state, served as a surrogate endpoint biomarker in
correlating the adverse effects of elevated/increase blood
pressures on cardiovascular output. We definitely can’t place
all biomarkers as a surrogate end-point identifier, thus making
their identification a ‘Novel and Revered Tool and Technology
(NORET)’ of researches into the lavish use of biomarkers in
research as well as other analytical studies. In terms of
professionalism, biomarker seems to be growing at a slower
rate though it had been expressly useful in pre-clinical and
clinical studies for a considerable amount of time, and has
been a bed for which quality research though adamant, had
spread their heart-ached analysis of simpler and complex
physiological problem alike.

Body temperature is a comparative and common biomarker
for fever. Blood pressure is another comparative and first
sought after NORET for stroke indications and complications.
Cholesterol values are NORETs indicating coronary and
vascular diseases, and C-reactive protein (CRP) is another
thought of NORET for inflammation.

Resoundingly, biomarkers may include NORETs that can
assess the necessary and vital information concerning a
particular problem or complication. Digressing a little, we find
that in Perera and Weinstein’s and Naylor’s studies that as
complex and complicated the nervous system is and has been
in recent times, the wider and more advanced the NORETS
utilized in assessing the information about the Nervous boxthe
brain and related disease complications [16,17]. Among
such NORETs are assessing the blood or Cerebrospinal Fluid (CSF). These may involve measurements directly on biological
media (e.g., blood or cerebrospinal fluid). The biomarker in its
tailored parametric (chemical, physical and biological) capacity
can independently assess the growth and development of the
disease, likewise the receptive effects of the administered
management.

With these whelming explanations made easy, biomarkers
are simply any kind of indicator that gives an accurate or near
accurate diagnosis of certain physiologic problems and in this
study, T2D.

Characteristics of Biomarkers

Among the labelled characteristics of an ideal biomarker
are:

• Safety and easy to measure (Quality over Quantity-Qua/
Quo).

• Affordability.

• Proven treatment to modify any given set of biomarker(s).

• Consistency irrespective of personality.

• Sensitivity and specificity.

Exceptional predictive value(s)

Describing briefly the features above, Pharma Matters
White Paper, in a comprehensive study noted that in all
patients with a disease condition, a positive result can be
determined with the specificity and sensitivity of the test [18].

In determining the biomarker requisite for T2D, I quickly
hover around the prevalence of other disease conditions and
their identifiable biomarkers for easy navigation through this
study. We seldom experience people or individuals with long
term illness requiring long term medications with less accurate
diagnosis of the persistent conditions especially in African
countries and other parts of the world. With the favourable
hand of biomarkers and NORETs, diseases can be effectively
diagnosed and proffered suitable treatments [20]. Diseases
like Alzeimer and rheumatoid arthritis which often times starts
off with an undetectable symptom stage until it becomes
seriously hurting, in these instances, biomarkers have helped
to quickly identify them as well as individuals susceptible to
their complications.

For a biomarker to be successfully utilized, the presented
sample material(s) which could be blood sample, urine or even
saliva must be fast and like oil drop on a white cloth for easy
examination and commencement of treatment. Hence proper
consultation process can immediately ensue for patients
already diagnosed. A rapid test, which delivers a result after
only a few minutes, is optimal. This makes it possible for the
physician to discuss with the patient how to proceed and if
necessary to start treatment immediately after the test.

Pathophysiology of type 2 diabetes

Already possessing a glimpse or two about the
metabolomics for biomarkers especially for the T2D, I subtly
digress into the pathophysiology of this study disease. As
important as it is hitting the nail right on point, it is essential I
reel in the intrigue behind T2D. We definitely realize that the
prevalence of T2D is as a result of progressive depletion in
glucose tolerance until it finally results in diabetes. What we
both should also remember is that T2D is and can be detected
on the basis of sporadically increased HbA1c level, leading to
IR and pancreatic β-cell malfunctioning.

Expressly evaluating older studies, I had realized the basic
conspiracy in the pathophysiologic defects in patients with
T2D; Impairment, Deterioration, Genetic Re-wiring and
Environmental familiarities.

A long time ago, noted that sporadically increased levels of
saturated fatty acids (FAs) could damage and continuous the
steady secretion of insulin leading to a significantly low
glucose tolerance [21]. Supporting Swinburn et al. and Lillioja
et al. [22], noted in another comprehensive study, that
damaged and continuous secretion of insulin examines T2D;
we fill in the blank spaces and proffer effective measures
against such defects. In the 70’s had noted then that certain
impairment in the secretion of insulin are as a result of
reduced/deteriorating sensitivity of the glucose (G) receptors
responsible for conveying the glucose signal to trigger insulin
release [23]. Genetic and environmental factors are the main
determinants of insulin secretion. Pimenta et al. [24]
confidently noted that the genetic and environmental factors
determine the secretion of insulin.

The issues surrounding biomarkers in health and diseases,
have expressly increased, yet biomarkers in field applications
had face a resilient wall trying to first combat and settle the
dispute between statistically effective studies carefully
moderating clinical problems and complications [25,26].

Biomarkers for T2d prediction

Generally, predicting diabetes has been of concern to many
researchers and scientists all over the world. However there
has been some new interventions regarding blood samples as
biomarkers becoming even more and more complex by the
day, but researchers an scientists need slated laws which
points the scientists towards clinically analysing diabetes. In
this paper, I delve into some standard areas that had suffered
little or no feathered heart concentration as far as T2D and its
health complications are concerned. However these areas should not be given a one glance consideration but a nicely
dished salad attention. They are as follows:

• First and foremost, we label the severity of T2D to better
provide the necessary dispensation for patients/individuals at
death’s door (stroke/heart attack) by desperately assessing
CVD complications, which on its own must be as refined as
liquid gold. On the contrary, diagnosis of diabetes which is
defined based on a blood sampling analysis for the various
complications of diabetes can always be repeated as long as
the individual still portrays some persistently increase risk
complications. Prediction of T2D in these contrasting
situations becomes unfailingly less important or critical.

• In a study, extensively noted and reported that at receiver
operating characteristics (ROC) of about 0.80 are possible
indicators for diabetes at simplified risk score such as Body
mass index (BMI), age, family histoire of diabetes, even age
[27]. Noting this, health care professionals can be steered thus
to naturally selecting suitable candidates for blood sampling
tests for T2D. Still on this note, Wannamethee et al. [28] noted
that simple risk scores for diabetes anywhere around the
world can be easily determined, and once taken up; the
exclamation in the Einstein’s light bulb is to determine what
the cut-points are for proceeding to a blood test.

• In a 2011 study, Wannamethee et al. [29], also noted that
HbA1c in close combination with other simple parameters
under the risk score ROC would better increase and enhance
future prediction of diabetes as well as T2D. However,
individuals with reduced HbA1c values should be considered at
potential risk of future diabetes as well as T2D, and quickly
proffered a composite and conducive lifestyle intervention [2].

• Finally, there is the need to statistically and significantly
relate cardiovascular diseases and diabetes risk screening
because nowadays, both go hand in hand building bridges
(more or less a catch 22 situation). Risk screening and
complications of diabetes has been a family chat for health
care professionals over every centre table discussion, but
rarely has these resolutions by the years been implemented
given its ball and chain complexity and the necessity for
continuous tests. Where there’s a seed, there’s hope, and the
initiation of HbA1c as a NORET for the diagnosis and prognosis
of diabetes has paved way to further growing this seed of faith
to advancing diabetes analysis and checkmating risk
complications and identifications. HbA1c testing does not
require fasting or denial of food, thus providing room for
constant and steady 24/7 screening for diabetes. Afterall, Di
Angelantonio [8] had noted that non-fasting lipid reports were
presented as would fasting lipid reports for CVD risk
prevention. Interestingly, Griffin et al. [12] noted in their study
that an earlier screening of diabetes would lesson CVD risk
complications and increase the chances of applying better
improved lifestyle practices. This suggestion is speculative, but,
clearly, picking up diabetes sooner after HbA1c crosses the
diagnostic threshold could have multiple advantages for
patients.

Biomarkers for T2d, complications, treatment
guidance

A snail and shell relationship exists between the available
diabetes treatment, HbA1c value indicators, ranging lipid
levels, correlating cardiac outcomes, and likely survival. This
symbiotic relationship surpasses the available ideas and ideals,
placing a limiter to comprehending their interactions and
possible workings [30,31].

Scientific assumptions regarding the reliability of biomarker
reports on a peculiar disease are sometimes regarded as a half
arms’ worth. Khaw et al. [32] had assumed in a comprehensive
study using the HbA1c value, that serious regulation of blood
glucose would in its own way reduce the risk complications of
diabetes as well as T2D complications, as documented by the
U.K Prospective Diabetes Study [33]. Due to the swell rates of
CVD in patients with T2D, both background and underground
studies have tried to correlate the effects of sufficient glycemic
control over CVD risks and complications but to no avail
[34-36].

Conclusion

Closely observing the tethering nature of biomarkers and
their susceptible efficiency, there is still a lot of work to be
accomplished in the field of biomarkers as well as its
diagnostic use in the prognosis of diabetes mellitus as well as
its risk complications. This study as well as other related
studies had shown some of the clinical correlation of
biomarkers in the possible identification of T2D. In this study
also, we had diversified our minds to the various complications
of T2D without highlighting the relative effects in women
population. This study shows how possible it is to quickly and
safely acquire relevant data on the variant functioning of
individual metabolites that rustles glucose tolerance and
insulin sensitivity. Here we realize that the relationship
between increased glucose concentration and T2D were
seriously at loggerheads. The biological features of these
related variants have been like searching for a tiny pin in hay
stack-challenging. In conclusion, I have identified some NORET
biomarkers (e.g. the sweet taste of urine, the receiver
operating characteristics (ROC) of about 0.80 and HbA1c) that
have been used in previous and continuous studies for
assessing the risks and development of diabetes, T2D as well
as their complications since these NORETs have in times past
and continuously help predict the onset of T2D and
consequently diagnosis and fast-racing prognosis before the
coming rains.

Ron Zimmer MA (2008) Evaluation and Regulation of Biomarkers A Public Health Perspective PHG Foundation OECD Workshop on Policy Issues for the Development and Use of Biomarkers in Health Wellcome Trust Conference Centre Hinxton..